Grand Rounds

1. Grand Rounds Brett Mueller, D.O., Ph.D. December 15, 2017

2. Patient Presentation CC Droopy left eyelid HPI 28 year-old African American female with no significant PMH presents with a droopy left eyelid for 5 months. States that the eyelid becomes more droopy throughout the day. Mentions having intermittent double vision.

3. History (Hx) Past Medical Hx: none Past Surgical Hx: none Meds: none Allergies: NKDA Social Hx: none

4. External Exam

5. Anterior Segment Exam

6. Posterior Segment Exam

7. External Exam Looking Straight Start of Levator Exhaustion Test 2 minutes of Levator Exhaustion Test

8. 5 min Ice Pack Test

9. Assessment 28 year-old African American female with unilateral ptosis and diplopia that worsens with ocular motility • Diagnosis • Ocular myasthenia gravis

10. Plan • Obtain • Anti-Acetylcholine receptor antibody • CT of the chest to rule out thymoma • Therapy • Pyridostigmine

11. 1 month later Start of Levator Exhaustion Test 2 minutes of Levator Exhaustion Test

12. Myasthenia Gravis (MG) • First described in 1672 by Thomas Willis, and the term “Myasthenia Gravis pseudo-paralytica” was coined 1895 • First treatment was performed in 1934 by Mary Walker, MD • Felt the disease was similar to curare toxicity and treated with physostigmine

13. Myasthenia Gravis • Autoimmune disease resulting in muscle fatigability and weakness • Symptoms improve with rest • Main ophthalmic complaints are: ptosis, diplopia, and extra-ocular muscle palsies

14. Ocular Myasthenia Gravis (OMG) • 85% of patients presenting with only ocular signs and symptoms of myasthenia graves (MG) will develop systemic MG within 2 years of presentation • However, after 2 years 90% of people who have OMG will not develop systemic MG

15. Epidemiology • Affect any age group and show no geographic predilection • Incidence: 0.04 - 5/100,000 per year • Prevalence: 0.5 - 12.5/100,000 per year

16. Demographics • OMG and MG differ with respect to the demographics of the affected population • MG is a 3:2 female to male ratio • OMG affects males more • Females that are affected typically have a mean age of 28 while men have a mean age of 42.

17. Clinical Presentation • Vary depending on which muscles are affected and can have variable muscular weakness and fatigability • Most common signs are ocular (50% of the time) which include: • Ptosis • Incomitant strabismus • External ophthalmoplegia

18. Clinical Presentation • Cogan Lid twitch • Hering’s law of equal innervation is typical of myasthenic ptosis

19. Clinical Presentation • Variable muscle weakness • Fatigability of the muscles of • Mastication • Facial Expression • Speech • Neck Extensors • Proximal Limb muscles • Respiratory muscles

20. Diagnosis • Edrophonium (Tensilon)Test: Need to have atropine on hand • Repetitive Nerve Stimulation: 95% specificity • + in 75% of patients with MG • + in 50% of patients with OMG • Single Fiber EMG: 88-99% sensitivity for ocular myasthenia

21. Diagnosis • Ice Test • Serum anti-acetylcholine receptor antibody titer • Present in 85-90% of MG • Present in 50% of OMG • Serum anti-muscle-specific kinase antibody titer

22. Differential Diagnosis • Lambert-Eaton Myasthenic Syndrome • Anything that can cause ptosis: • Intracranial lesion • Aneurysm • Thyroid eye disease can occur in conjunction with MG in up to 5% of patients

23. Pathogenesis • Antibodies against the acetylcholine receptor sites at the post-synaptic neuromuscular junction • Muscle becomes weak due to impaired transmission

24. Treatment • Medical Therapy • Acetylcholinesterase inhibitors • Oral Steroids • Immunomodulators

25. Treatment • Surgery • Surgical removal of the thymus gland • 66% of patients have thymic hyperplasia (thymomas) • 10% of patients have thymic tumors

26. Complications • Occur when larger muscle groups become involved • Dysphagia and dyspnea can lead to respiratory compromise and death • Myasthenic crises

27. Prognosis • Fair as long as symptoms are well controlled • Poor if larger muscle groups involved with respiration or swallowing become involved • 85% of patients who develop OMG will develop MG within 2 year

28. Conclusions • Ocular manifestations can be the presenting complaint in 50% of patients • Patients with OMG have an 85% chance to progress to MG within 2 year. But if a patient has OMG for more than 2 years, they only have a 10% chance of progressing to MG • Lethal when patients develop dyspnea or dysphagia

29. References • Kanski’s Clinical Ophthalmology A systemic Approach, Eighth Edition. Brad Bowling • Neuro-ophthalmology, BSCS • Oculoplastics, BSCS • E. Kerty, A. Elsais, Z. Argov, et al.EFNS/ENS guidelines for the treatment of ocular myasthenia gravisEur. J. Neurol., 21 (2014), pp. 687-693 • Conti-Fine BM, Milani M, Kaminski HJ. Myasthenia gravis: Past, present, and future. J Clin Invest. 2006;116:2843–54. • O’Brien MD. The miracle at St Alfege's: Seventy years on. J R Soc Med. 2007;100:257. • López-Cano M, Ponseti-Bosch JM, Espin-Basany E, Sánchez-García JL, Armengol-Carrasco M. Clinical and pathologic predictors of outcome in thymoma-associated myasthenia gravis. Ann Thorac Surg. 2003;76:1643–9.  • Singhal BS, Bhatia NS, Umesh T, Menon S. Myasthenia gravis: A study from India. Neurol India. 2008;56:352–5.  • Grigg J. Extraocular muscles: Relationship of structure and function to disease. Aust N Z J Ophthalmol. 1999;27:369–70. • Sommer N, Melms A, Weller M, Dichgans J. Ocular myasthenia gravis. A critical review of clinical and pathophysiological aspects. Doc Ophthalmol. 1993;84:309–33. • Neuro-Ophthalmology, Section 5. Basic and Clinical Science Course, AAO, 2009-2010. • Miller NR & Newman MJ. The Essentials: Walsh & Hoyt's Clinical Neuro-Ophthalmology. 5th edition. Lippincott:1999. • Burkat, CN., et al., Myasthenia Gravis. Eyewiki. Ed. Burkat, CN. 2017